1. Field of the Invention
The present invention relates to percutaneous or trans-mucosal absorption enhancers and preparations containing said enhancers.
2. Related Art Statement
Conventionally, oral dosage or injection has been widely employed to administer drugs. But, recently percutaneous or trans-mucosal dosage forms have been attracting attentions not only to obtain local effect but also to get systemic effect of the drugs.
Advantages for percutaneous or trans-mucosal medication are as follows:
(1) it is convenient for a patient to apply it at high home and to remove promptly if any side effect like toxic symptoms would appear; PA1 (2) it is easily applicable to patients who are incapable of oral administration due to the poor degultution ability, especially to infants and aged persons; PA1 (3) it shows high bioavilability of beneficially effective constituents because it is not subjected to first pass effect (metabolism) at liver which is observed in oral administration; PA1 (4) it is easy to attain sustained release as well as local application, and, both local and systemic effect may be obtained when applied on the local skin diseases such as cancer and herpes; and PA1 (5) high patient compliance is obtained with the medication.
Contrary to the advantages as stated above, however, percutaneous or trans-mucosal medication has a big shortcoming that absorption of beneficially effective constituents through skin and mucous membranes is very poor compared with oral administration and injection. Especially when drugs are water soluble, this shortcoming becomes prominent. For enhanced absorption of effective drugs through stratum corneum of the skin, many studies have been done on various percutaneous or trans-musocal absorption enhancers.
Alcohols and glycols; urea derivatives hyaluronic acids; N, N-dimethyl foramide (DMF) and dimethyl sulfoxide (DMSO)), both being non-protic solvents; and surfactants (especially anionic surfactants); have been reported as substances having percutaneous or trans-musocal absorption facilitation. The most marked substance in recent years is (1)-dodecylazacycloheptane-2-one (trade name: AZONE) developed by Nelson Co., Ltd., USA.
Among the above enhancers, however, alcohols and glycols are not confirmed to be effective in percutaneous or trans-musocal facilitation and there are many reports expressing that they are ineffective. There are several cumbersome problems for the relation between the enhancing effect and their concentration in preparation. With respect to DMSO its absorption enhancing effect depends largely upon its concentration, and it is considered to be almost ineffective with a concentration lower than 50%. Further it shows adverse effects on eyes and also has side effects on skin, consequently it is not practically used until now. As for urea derivatives, hyaluronic acids, N, N-dimethyl foramide and surfactants, their absorption enhancing effect is remarkably poor as compared with that of dimethyl sulfoxide.
1-dodecylazacycloheptane-2-one shows relatively high absorption enhancing effect even when applied with low concentration but it is a quite novel substance and its safety is not yet confirmed.
Thus percutaneous or trans-mucosal absorption enhancers already known are unsatisfactory in view of the effect and safety so that development of safe and effective absorption enhancers for percutaneous or trans-mucosal preparation has been demanded increasingly.